The Macaca Fascicularis (irus) monkey has been developed as an experimental model for the study of obstructive atherosclerosis of the coronary and peripheral arteries. Severe stenosing lesions have been induced reproducibly by a high cholesterol diet for 18 months with the coronary lesions being located in the proximal epicardial coronary arteries leading to myocardial ischemia as indicated by ECG and myocardial necroses and fibroses. A research plan is proposed to study the morphological and biochemical fate of the experimental atherosclerosis in aorta, coronary and peripheral arteries as well as to test the myocardial function and peripheral circulation in (1) monkeys on conditioning exercise for 36 months with the last 18 months being on the atherogenic diet, (2) monkeys on the atherogenic diet for 36 months without exercise, (3) monkeys on the atherogenic diet for 36 months with the last 18 months exercising moderately. The data will be compared to those from animals on a non-atherogenic diet with and without conditioning exercise for 36 months. All animals will be stress exercised at months 0, 18 and 36 and their performance (including ECG by radiotelemetry) and number of possible sudden deaths will be compared. At the same time an evaluation will be made on changes in the luminal diameter of coronary and peripheral arteries by in vivo angiography and on the effect of these changes on the function of the myocardium and the peripheral circulation. ECG's and angiographic findings will be correlated to serum lipids, sugar, uric acid and myocardial enzymes. These in vivo findings will be correlated with the content and composition of arterial lipids, connective tissue and calcium as well as with morphological changes of aorta, coronary and peripheral arteries (including luminal diameter) and myocardia. The proposed studies may help to clarify whether exercise is capable of (1) altering the natural history of atherosclerosis, (2) influencing the efficiency of myocardial and peripheral circulation (collaterals, thrombosis), (3) improving myocardial function. The data obtained may provide helpful insights with regard to the uncertainties whether exercise can influence favorably atheroschlerosis and coronary heart disease and should be recommended for treatment.